HBOT & Stem Cells

Hyperbaric oxygen therapy (HBOT) has robust effects on stem cell biology, including mobilization, proliferation, differentiation, and regenerative potential, with evidence spanning human, animal, and in vitro studies.

Stem Cell Mobilization:

HBOT consistently increases the number of circulating stem/progenitor cells (SPCs), particularly CD34+ cells, in both healthy individuals and patients. Human studies show that a single HBOT session can double circulating CD34+ cells, and repeated sessions can increase levels up to eightfold, with enhanced colony-forming capacity and expression of key regulatory proteins such as hypoxia-inducible factors (HIFs) and thioredoxin-1.[1][2] The mobilization mechanism is nitric oxide (NO)-dependent: HBOT stimulates NO synthase activity in bone marrow, which triggers stem cell release into the bloodstream. This effect is durable and dose-dependent, with higher oxygen pressures (2.5 ATA vs. 2.0 ATA) yielding greater mobilization.[1][2] Recent work also shows that hyperbaric air (not just pure oxygen) can mobilize SPCs in humans, suggesting a hormetic dose-response and broadening therapeutic potential.[3]

Stem Cell Proliferation and Differentiation:

HBOT enhances stem cell proliferation in various tissues. In animal models, HBOT increases intestinal stem cell turnover via the mTORC1/S6K1 signaling pathway, directly linking oxygen tension to stem cell activity.[4] In diabetic mice, HBOT boosts proliferation and angiogenic capacity of Wharton’s Jelly mesenchymal stem cells (WJ-MSCs), improving wound healing and tissue repair.[5] In vitro, HBOT increases viability, proliferation, and differentiation of human adipose-derived stem cells, with a shift toward adipogenic lineage and reduced TGF-β secretion.[6] For gingival mesenchymal stem cells, a single HBOT exposure promotes anti-inflammatory, regenerative, and differentiation effects, while repeated exposures may induce cellular stress, highlighting the importance of protocol optimization.[7]

Regenerative Potential and Clinical Implications:

HBOT’s ability to mobilize and activate stem cells translates to enhanced tissue repair and regeneration. In diabetic patients with chronic wounds, HBOT not only increases circulating vasculogenic stem cells but also boosts their recruitment to wound sites and upregulates intracellular regulatory proteins (HIFs, Trx-1), supporting improved healing outcomes.[8] HBOT also stimulates vasculogenic stem cell growth and differentiation in vivo, activating redox-sensitive pathways (thioredoxin, HIFs, VEGF, SDF-1) that drive angiogenesis and tissue regeneration.[9] These effects are supported by clinical guidelines, which recognize HBOT’s role in stimulating progenitor stem cell mobilization and angiogenesis as part of its therapeutic mechanism in chronic limb-threatening ischemia and wound healing.[10]

Summary:

HBOT mobilizes stem/progenitor cells via NO-dependent mechanisms, enhances their proliferation and differentiation, and improves their regenerative capacity in both experimental and clinical settings. These effects are dose-dependent and protocol-sensitive, with implications for tissue repair, wound healing, and regenerative medicine. Ongoing research is refining optimal dosing and exploring broader applications in stem cell-based therapies.

References

1. Stem Cell Mobilization by Hyperbaric Oxygen. Thom SR, Bhopale VM, Velazquez OC, et al. American Journal of Physiology. Heart and Circulatory Physiology. 2006;290(4):H1378-86. doi:10.1152/ajpheart.00888.2005.

2. CD34+/CD45-dim Stem Cell Mobilization by Hyperbaric Oxygen - Changes With Oxygen Dosage. Heyboer M, Milovanova TN, Wojcik S, et al. Stem Cell Research. 2014;12(3):638-45. doi:10.1016/j.scr.2014.02.005.

3. Hyperbaric Air Mobilizes Stem Cells in Humans; A New Perspective on the Hormetic Dose Curve. MacLaughlin KJ, Barton GP, Braun RK, et al. Frontiers in Neurology. 2023;14:1192793. doi:10.3389/fneur.2023.1192793.

4. Hyperbaric Oxygen Treatment Increases Intestinal Stem Cell Proliferation Through the mTORC1/S6K1 Signaling Pathway in Mus Musculus. Casanova-Maldonado I, Arancibia D, Lois P, Peña-Villalobos I, Palma V. Biological Research. 2023;56(1):41. doi:10.1186/s40659-023-00444-3.

5. Hyperbaric Oxygen Increases Stem Cell Proliferation, Angiogenesis and Wound-Healing Ability of WJ-MSCs in Diabetic Mice. Peña-Villalobos I, Casanova-Maldonado I, Lois P, et al. Frontiers in Physiology. 2018;9:995. doi:10.3389/fphys.2018.00995.

6. The Effect of Hyperbaric Oxygen Therapy on Human Adipose-Derived Stem Cells. Yoshinoya Y, Böcker AH, Ruhl T, et al. Plastic and Reconstructive Surgery. 2020;146(2):309-320. doi:10.1097/PRS.0000000000007029.

7. Effect of Hyperbaric Oxygen and Inflammation on Human Gingival Mesenchymal Stem/Progenitor Cells. Tölle J, Koch A, Schlicht K, et al. Cells. 2023;12(20):2479. doi:10.3390/cells12202479.

8. Vasculogenic Stem Cell Mobilization and Wound Recruitment in Diabetic Patients: Increased Cell Number and Intracellular Regulatory Protein Content Associated With Hyperbaric Oxygen Therapy. Thom SR, Milovanova TN, Yang M, et al. Wound Repair and Regeneration : Official Publication of the Wound Healing Society [And] the European Tissue Repair Society. 2011 Mar-Apr;19(2):149-61. doi:10.1111/j.1524-475X.2010.00660.x.

9. Hyperbaric Oxygen Stimulates Vasculogenic Stem Cell Growth and Differentiation in Vivo. Milovanova TN, Bhopale VM, Sorokina EM, et al. Journal of Applied Physiology (Bethesda, Md. : 1985). 2009;106(2):711-28. doi:10.1152/japplphysiol.91054.2008.

10. Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia. Conte MS, Bradbury AW, Kolh P, et al. Journal of Vascular Surgery. 2019;69(6S):3S-125S.e40. doi:10.1016/j.jvs.2019.02.016.